The effect of injecting either iodoacetate or iodoacetate-treated thymocytes from leukemic AKR mice (ITC) on the humoral immune response of preleukemic AKR mice (8 or 12 weeks old) to sheep erythrocytes (SRBC) was assessed. Six days after a single injection of iodoacetate, or ITC (viable or nonviable), mice were administered sheep erythrocytes. Four days later, spleens and thymuses were assayed for total numbers of plaque-forming cell (PFC). Significant increases in total numbers of splenic (PFC) were noted when compared with untreated controls. Histopathological examinations of the spleens revealed large numbers of mature lymphoid cells in the red pulp areas. In a companion study, AKR mice (6 to 7 months old) were treated with multiple doses of iodoacetate (5 injections at 10 day intervals). An increase in mean survival time of 15 days was observed in comparison with a placebo group. Additionally, there was an increase in the numbers of (PRC) at all test intervals. In an effort to characterize the role of the T lymphocyte in the model AKR spontaneous leukemia, rabbit anti-mouse-brain-associated-theta serum (BA-theta) was tested for its effect on the immunological responsiveness of preleukemic and leukemic AKR mice to sheep erythrocytes. Leukemic mice received daily injections for a total of 3, and pre-leukemic mice daily injections for a total of 3 or 5. It was found that the administered antiserum was immunosuppressive in vivo, and that greater immunosuppression was noted in the preleukemic than in the overtly leukemic animals.